Short-Term Association between Sulfur Dioxide and Mortality: A Multicountry Analysis in 399 Cities

BACKGROUND: Epidemiological evidence on the health risks of sulfur dioxide ([Formula: see text]) is more limited compared with other pollutants, and doubts remain on several aspects, such as the form of the exposure–response relationship, the potential role of copollutants, as well as the actual risk at low concentrations and possible temporal variation in risks. OBJECTIVES: Our aim was to assess the short-term association between exposure to [Formula: see text] and daily mortality in a large multilocation data set, using advanced study designs and statistical techniques. METHODS: The analysis included 43,729,018 deaths that occurred in 399 cities within 23 countries between 1980 and 2018. A two-stage design was applied to assess the association between the daily concentration of [Formula: see text] and mortality counts, including first-stage time-series regressions and second-stage multilevel random-effect meta-analyses. Secondary analyses assessed the exposure–response shape and the lag structure using spline terms and distributed lag models, respectively, and temporal variations in risk using a longitudinal meta-regression. Bi-pollutant models were applied to examine confounding effects of particulate matter with an aerodynamic diameter of [Formula: see text] ([Formula: see text]) and [Formula: see text] ([Formula: see text]), ozone, nitrogen dioxide, and carbon monoxide. Associations were reported as relative risks (RRs) and fractions of excess deaths. RESULTS: The average daily concentration of [Formula: see text] across the 399 cities was [Formula: see text] , with 4.7% of days above the World Health Organization (WHO) guideline limit ([Formula: see text] , 24-h average), although the exceedances occurred predominantly in specific locations. Exposure levels decreased considerably during the study period, from an average concentration of [Formula: see text] in 1980–1989 to [Formula: see text] in 2010–2018. For all locations combined, a [Formula: see text] increase in daily [Formula: see text] was associated with an RR of mortality of 1.0045 [95% confidence interval (CI): 1.0019, 1.0070], with the risk being stable over time but with substantial between-country heterogeneity. Short-term exposure to [Formula: see text] was associated with an excess mortality fraction of 0.50% [95% empirical CI (eCI): 0.42%, 0.57%] in the 399 cities, although decreasing from 0.74% (0.61%, 0.85%) in 1980–1989 to 0.37% (0.27%, 0.47%) in 2010–2018. There was some evidence of nonlinearity, with a steep exposure–response relationship at low concentrations and the risk attenuating at higher levels. The relevant lag window was 0–3 d. Significant positive associations remained after controlling for other pollutants. DISCUSSION: The analysis revealed independent mortality risks associated with short-term exposure to [Formula: see text] , with no evidence of a threshold. Levels below the current WHO guidelines for 24-h averages were still associated with substantial excess mortality, indicating the potential benefits of stricter air quality standards. https://doi.org/10.1289/EHP11112